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Biomedical subjects

K K Midha

Publications and source records attributed to K K Midha.

At least 181 records · Page 10Linked to original sources
PubMed1983

Correlation of fluphenazine plasma levels versus clinical response in patients: a pilot study.

Five schizophrenic patients (diagnosed using Research Diagnostic Criteria) under treatment with intramuscular fluphenazine decanoate or oral fluphenazine dihydrochloride had serial plasma fluphenazine and plasma prolactin levels determined by a direct radioimmunoassay method. Clinical state was assessed utilizing the Global Assessment Scale and the Extrapyramidal Symptoms-Neurological Rating Scale. There was no correlation between clinical state and plasma fluphenazine or prolactin levels. All patients under treatment with the depot preparation remained clinically stable with serum fluphenazine levels between 1 and 3 ng/ml. In one patient, who received an intramuscular dose of fluphenazine decanoate, plasma levels were determined using direct radioimmunoassay, extraction followed by radioimmunoassay and gas liquid chromatography-mass spectrometry. There were good correlation between the three methods.

Administration, Oral↗
PubMed1983

Radioimmunoassay for prochlorperazine in human plasma.

A new sensitive, specific, and rapid radioimmunoassay procedure for the determination of plasma concentrations of the antiemetic drug prochlorperazine is described. The assay enables the quantitation of 31 pg of the drug in 200 microliters of plasma with a coefficient of variation of approximately 2%. Except for N-desmethylprochlorperazine, the antiserum did not cross-react with the available metabolites tested. Also there was no cross-reactivity with the tricyclic antidepressants and antianxiety agents commonly co-administered with the drug. The method is suitable for single-dose pharmacokinetic and bioavailability studies. It should be adequate for the therapeutic monitoring of the drug in patients.

Animals↗
PubMed1983

Kinetics of oral trifluoperazine disposition in man.

The disposition of trifluoperazine (TFP) was studied in five healthy volunteers following oral administration of a 5 mg tablet. Using a very sensitive GC-MS technique plasma TFP concentrations were measured up until 24 h following drug ingestion. Peak plasma concentrations varied widely (range 0.53-3.09 ng ml-1) and were reached 2.8 +/- 0.5 h following ingestion of the TFP tablet. The apparent terminal elimination half-life of TFP was 12.5 +/- 1.4 h. The area under the plasma concentration-time curve differed widely between subjects (range: 5.9-17.6 ng ml-1 h) suggesting large individual differences in the extent of presystemic TFP elimination.

Administration, Oral↗
PubMed1983

Identification of new secondary metabolites of methoxyphenamine in man.

Metabolites of methoxyphenamine were examined in the urine of three healthy human volunteers. The metabolites were separated by g.l.c. and identified by comparison of their chromatographic and mass-spectrometric behaviours with those of authentic synthetic compounds. 5-Hydroxy-2-methoxy-N-methylamphetamine, a metabolite previously identified by indirect methods, was conclusively identified by comparison with the now-available authentic synthetic material. In addition, three new metabolites of methoxyphenamine were identified--5-hydroxy-2-methoxyamphetamine, 2-methoxyphenylacetone and 5-hydroxy-2-methoxyphenylacetone.

Chromatography, Gas↗
PubMed1983

A study of the kinetics of chlorpromazine sulfoxide by a specific radioimmunoassay after a single oral dose of chlorpromazine in healthy volunteers.

Antibody specific for chlorpromazine sulfoxide (CPZSO) was produced in rabbits immunized with a hapten-bovine serum albumin conjugate, which was prepared by linking the 10-alkyl side chain of CPZSO to the protein molecule via a 2-carbon bridge. A simple radioimmunoassay was developed which can measure less then 20 pg of CPZSO in plasma. The assay has adequate specificity so that isolation of CPZSO is unnecessary. It was used together with a previously developed chlorpromazine (CPZ) radioimmunoassay to determine the concentrations of CPZ and CPZSO in plasma samples from five healthy volunteers after they had received a single 50-mg oral dose of CPZ. The plasma level data reported here support the previous findings that a significant portion of CPZ is metabolized to CPZSO during presystemic absorption. There are, however, differences to those previously reported in the plasma concentration ratios of CPZSO to CPZ. The possible reasons for these differences are discussed.

Administration, Oral↗
PubMed1982

High-performance liquid chromatographic assay of indomethacin and its application in pharmacokinetics in healthy volunteers.

A new sensitive high-performance liquid chromatographic method for indomethacin from plasma on a reversed-phase column (C18) has been developed. The method involves precipitation of plasma with perchloric acid followed by diethyl ether extraction. The assay is quantitative down to 0.25 microgram ml-1 from a 200-microliters aliquot of plasma with a detection limit of 0.1 microgram ml-1 and a recovery of approximately 90%. The method was applied to single-dose studies with volunteers under various dietary restrictions. The results of these studies indicated that intrasubject variability within these regimens may be as important a factor as the intersubject variability already documented for this drug. These results have important implications in the determination of bioavailability and pharmacokinetic parameters of this drug.

Chromatography, High Pressure Liquid↗
PubMed1982

Gas chromatographic--mass spectrometric procedure for the quantitation of chlorpromazine in plasma and its comparison with a new high-performance liquid chromatographic assay with electrochemical detection.

A gas chromatographic--mass spectrometric assay using selected ion monitoring is compared with a high-performance liquid chromatographic assay using an electrochemical detector for single-dose studies of the psychotherapeutic phenothiazine drug chlorpromazine. Measurements were made after extraction of chlorpromazine and the internal standard, prochlorperazine, from basified plasma with an isopropanol--pentane solvent mixture. Following evaporation of the organic solvents the residue was reconstituted in a small volume of methanol and subjected to gas chromatographic--mass spectrometric selected ion detection. The residual sample was then evaporated and made up in a larger volume of acetonitrile and analyzed by high-performance liquid chromatography using an electrochemical detector. These specific methods display excellent correlation for plasma concentration determinations in the range of 0.25-10 ng ml-1 and will allow for the study of the pharmacokinetics of chlorpromazine following single low doses of the drug.

Chlorpromazine↗
PubMed1982

A gas chromatographic mass spectrometric assay for plasma trifluoperazine concentrations following single doses.

A gas chromatography mass spectrometric assay using selected ion monitoring is described which permits the determination of trifluoperazine in plasma at concentrations ranging from 0.078 to 5.0 ng ml-1. It relies on the extraction of trifluoperazine and the internal standard, prochlorperazine or the tetradeuterated analogue of trifluoperazine, from basified plasma with a n-pentane/2-propanol solvent mixture. Following the evaporation of organic solvent, the residue is reconstituted in a small volume of methanol. Suitable aliquots were analysed by the combined technique of gas chromatography/electron impact mass spectrometry with a data system. The described procedure is specific and enables the quantitation of 78 pg ml-1 of the drug with a coefficient of variation less than 7%. The method has demonstrated sufficient sensitivity to permit pharmacokinetic and bioavailability studies after a single 5 mg oral dose.

Biological Availability↗
PubMed1982

A GLC-nitrogen phosphorous detector assay for trifluoperazine in plasma.

A GLC-nitrogen phosphorous detector (NPD) method for the quantitative determination of trifluoperazine in plasma is described. It depends on an organic extraction of trifluoperazine and the internal standard prochlorperazine from basified plasma. Following the extraction, the organic solvent is evaporated to dryness and the residue is reconstituted in a small volume of methyl alcohol. GLC analysis of aliquots of the methanolic solution using a NPD permitted the determination of 0.5 ng/ml of trifluoperazine in plasma. Standard curves for trifluoperazine over a concentration range of 0.5 to 15 ng/ml of plasma were linear with an overall variation coefficient of 5.3%. In isolated samples obtained from a normal healthy volunteer, application of this method to plasma concentration determinations after oral administration of a 5-mg trifluoperazine tablet, is demonstrated and compared with the concentrations obtained by GLC-mass spectrometry and radioimmunoassay procedures.

Chemical Phenomena↗
PubMed1982

Identification of phenolic acids in human urine by ion monitoring.

1. Two-different double derivatization techniques and two different g.l.c. systems were used to separate isomeric phenolic carboxylic acids in normal human urine. 2. Carboxylic acids were converted into n-butyl esters and phenolic functions into trifluoroacetic acid esters. 3. n-Butyl trifluoroacetoxybenzoates were separated by g.l.c. and detected by mass spectrometric single-ion monitoring. 4. Trifluoroacetates were hydrolysed under mild conditions, and liberated phenolic groups were subjected to flash methylation. 5. n-Butyl methoxybenzoates were separated by g.l.c. and detected by flame ionization. 6. All derivatives were identified by comparison of retention times and mass spectra with those of authentic reference standards. 7. The urine of a normal vegetarian volunteer was examined. 8. The presence of meta- and para-hydroxybenzoic acids, vanillic acid and isovanillic acid was confirmed by unambiguous techniques.

Chromatography↗
PubMed1981

Bioavailability of 11 quinidine formulations adn pharmacokinetic variation in humans.

The bioavailabilities of eight quinidine sulfate, two gluconate, and one polygalacturonate formulations were compared, with one of the sulfate formulations as a reference (R) in a panel of 24 volunteers, according to a design comprising duplicate 6 x 6 Latin squares in two subject groups. Only one gluconate formulation (H) gave a significantly lower (p less than 0.05) area under the curve from 0 to 30 hr (AUC30), 90% or R, which was not as significant as AUC infinity (94% of R). Formulation H also gave a significantly lower peak concentration (Cmax) and a longer time to peak concentration (tmax) and generally exhibited some characteristics of sustained-release product. In addition, one product (F) gave a significantly higher Cmax while another formulation (D) gave a longer tmax. The wide range of dissolution times obtained with these products with three test conditions was not reflected in the AUC, Cmax, or tmax values obtained, except the Formulation H was consistently the slowest to dissolve. The terminal rate constants, expressed as t 1/2, of the 24 subjects gave an overall mean of 7.49 +/- 0.77 hr and ranged from 6.24 +/- 0.28 to 0.49 +/- 0.90 hr in individuals. The estimated total body clearance, with the assumption that the oral bioavailability was 70%, gave an overall mean of 4.22 +/- 1.05 and ranged from 2.49 +/- 0.28 to 6.42 +/- 0.70 mg/min/kg in individuals, demonstrating the wide range of quinidine disposition even in healthy subjects; this finding is in agreement with recently published results.

Adult↗
PubMed1981

High-performance liquid chromatographic assay for nanogram determination of chlorpromazine and its comparison with a radioimmunoassay.

A specific and sensitive high-performance liquid chromatographic (HPLC) method for the quantitative determination of plasma chlorpromazine concentrations is described. The procedure is capable of determining 1 ng of chlorpromazine/ml and is adequate for following plasma concentration-time profiles after 7-mg single intravenous doses. After a simple organic extraction of the drug and an internal standard (mesoridazine) from plasma, the organic layer was transferred to a vial and evaporated to dryness at 55 degrees under nitrogen. The residue was dissolved in 200 microliters of HPLC grade acetonitrile. Aliquots (70-100 microliters) were chromatographed, and the drug was quantitated in the range of 1-15 ng/ml of plasma using a fixed-wavelength UV detector. Plasma concentrations determined by the method were compared with those obtained by a previously reported radioimmunoassay specific for chlorpromazine and N-desmethylchlorpromazine. The two methods agreed favorably with a correlation coefficient of 0.993 and a slope of 0.994.

Chlorpromazine↗
PubMed1981

Radioimmunoassay for perphenazine in human plasma.

1 A new sensitive, specific and rapid radioimmunoassay procedure for the determination of plasma concentrations of the neuroleptic drug perphenazine is described. 2 The antiserum developed for perphenazine did not cross-react with most of the major metabolites of perphenazine nor the tricyclic antidepressants and antianxiety agents commonly co-administered with the drug. 3 The assay, based on the above antiserum, enabled the quantitation of 50 pg of the drug in 200 microliters of plasma with a coefficient of variation of about 8% and therefore should be applicable for single dose pharmacokinetic studies, as well as therapeutic monitoring of the drug in patients.

Animals↗
PubMed1981

Radioimmunoassay for trifluoperazine in human plasma.

1 A new sensitive and rapid radioimmunoassay procedure for the determination of the plasma concentrations of the neuroleptic drug trifluoperazine is described. 2 The antiserum developed for trifluoperazine cross-reacted with N-desmethyltrifluoperazine and 7-hydroxytrifluoperazine to the extent of 26 and 24% respectively but its cross-reactivity with commonly co-administered tricyclic antidepressants and antianxiety agents tested was negligible. 3 The assay, based on the above antiserum, enabled the quantitation of 50 pg of the drug in 200 microliters of plasma with a coefficient of variation of about 2% and therefore should be applicable for singly dose pharmacokinetic and bioavailability studies. It should be applicable to therapeutic monitoring of the drug in patients.

Animals↗